AACR: Merck, Kelun’s Anti-TROP2 ADC Shows Early Promise in Gastric Cancer

Merck research laboratories_iStock, hapabapa

Pictured: Merck Research Laboratories in South San Francisco, California/iStock, hapabapa

Preliminary Phase I/II data demonstrated that Merck and Kelun-Biotech’s TROP2-directed antibody-drug conjugate SKB264 can elicit promising disease control and even potentially extend survival among heavily pretreated patients with gastric or gastroesophageal junction cancer, according to an abstract presentation Tuesday at the 2024 American Association for Cancer Research annual meeting.

SKB264 achieved a 22% objective response rate in 41 patients who were evaluated for treatment response, nine of whom were partial responders. Disease control rate was 80.5%, with a median duration of response of 7.5 months.

In a subgroup of 24 patients who had been exposed to at least two prior lines of therapy and with more mature follow-up, SKB264 also appeared to boost survival. Median progression-free survival in this population was 3.7 months, while median overall survival (OS) reached 7.6 months. The 12-month OS rate was 32.6%.

SKB264 is an investigational antibody-drug conjugate (ADC) targeting the TROP2 cell surface protein, which is a well-validated target in gastric cancer and is associated with poor prognosis. The ADC’s toxic payload is a belotecan-derivative topoisomerase I inhibitor that causes DNA damage and triggers cell death.

The ADC also uses a novel linker that is cleaved by pH changes in the vicinity of the tumor and by enzymes inside the cancer cells, allowing the payload to exert its anti-cancer effect in a targeted manner.

“It is interesting to note the change in antitumor activity and safety profile that results from changing payloads and linkers, even among ADCs aiming at the same target,” Jordi Rodon, study lead author and associate professor of investigational cancer therapeutics at the MD Anderson Cancer Center, said in a statement.

“One of the big results of this trial is that, by using a different linker-payload combination, we did not see the interstitial lung diseases associated with other ADCs,” Rodon added.

MD Anderson Cancer Center said in Tuesday’s announcement that a global Phase III study is being planned to evaluate SKB264 in comparison to the current standard of care in patients with at least three prior lines of therapy in gastric or gastroesophageal junction adenocarcinomas.

Merck in 2022 exercised its option for worldwide rights—except in the Greater China region—to SKB264, which aside from gastric cancer is also being assessed in a Phase III study for triple-negative breast cancer and in a Phase II trial for non-small cell lung cancer and other advanced tumors. Merck and Kelun, a subsidiary of China-based Sichuan Kelun Pharmaceutical, forged an oncology partnership shortly after.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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